The prevalence of depression has risen by almost 50% worldwide from 1990 to 2017, leading to increased economic burden and reduced lifespans of those affected by an average of 12.7 years.1,2,3 This trend has necessitated research into treatments more effective than SSRIs and SNRIs, which are the most common antidepressants used today.4 Ketamine, an anesthetic drug with dissociative and hallucinogenic effects, alleviates depression symptoms far more rapidly than SSRIs, which take months to work, decreasing MARDS scores by almost eight more points than placebo 24 hours after treatment.10 Previous research has indicated that the R-enantiomer of ketamine improves mice outcomes in antidepressant-predictive tasks more effectively than S-ketamine.13 Additionally, data has demonstrated that (2R-6R)-HNK, an R-ketamine metabolite, is important for R-ketamine's antidepressant effects.14 OCD is often comorbid with depression and is often treated with SSRIs.7 Furthermore, since both disorders often exhibit reduced serotonin synthesis capacity, the two disorders may share similarities in mechanism.6,9 The study will assess the viability of the quinpirole-induced compulsive checking or QICC model for OCD treatment research, the effectiveness of R-ketamine at reducing compulsive behaviors in QICC mice compared to placebo and the SSRI paroxetine, and the role of the metabolite (2R-6R)-HNK in R-ketamine's efficacy in reducing compulsive checking behaviors in QICC mice. In this experiment, mice will be treated with either saline or quinpirole twice weekly for five weeks to create healthy control and QICC groups. When mice are treated with quinpirole, compulsive behaviors in mice such as frequent returns to specific places, shorter time intervals returning to preferred places, and fewer visits to non-preferred places are increased when compared to healthy controls.19 In these two groups, mice will be treated with either saline, the SSRI paroxetine, R-ketamine, or R)-d2-ketamine, an R-ketamine molecule altered to impede metabolism to (2R, 6R)-HNK. To monitor changes in compulsive checking behaviors, open-field tests will be performed on each mouse one hour, one day, and one week after treatment Additionally, changes in serotonin concentration in the raphé nuclei, the brain's primary area of serotonin production, will be tracked with microdialysis with analysis using HPLC-ECD. While R-ketamine, (R)-d2-ketamine, and paroxetine are all expected to reduce compulsive checking behaviors in QICC mice to levels similar to healthy control mice, R-ketamine is predicted to be the most effective. Similarly, while R-ketamine, (R)-d2-ketamine, and paroxetine are all expected to increase serotonin concentration in mice raphé nuclei, R ketamine is predicted to cause the greatest increase in serotonin concentration. If data indicates that R-ketamine is more effective than paroxetine at reducing compulsive checking behavior and increasing serotonin levels in QICC mice, R-ketamine should be considered in future research as a prospective OCD treatment. Furthermore, if R-ketamine is more effective than (R)-d2-ketamine at reducing compulsive checking behaviors and increasing serotonin concentration in QICC mice, (2R, 6R)-HNK may be important for R-ketamine's function as an OCD treatment.